Allergic asthma is the most common chronic disease of childhood in the United States. The role of exposure to allergens in asthma development is poorly understood. Our preliminary data suggest that while some aeroallergens may be risk factors, other allergens or their animal sources may be protective against asthma and allergy when encountered at the right dose, early in life. Immune mechanisms for early life allergen effects on later asthma development are uncertain. The established asthmatic response to allergens and other stimuli involves a complex interaction of T lymphocytes, B lymphocytes, and antigen-presenting cells, with the production of classic Th2 cytokines (e.g. interleukin (IL)-4, IL-13) and IgE, but also with production of non-Th2 cytokines such as IL-6 and TNF-alpha. We propose to extend our prospective longitudinal study of children of asthmatic/allergic parents to examine environmental influences on asthma and immune development, following our birth cohort into puberty, a period of significant transition when female asthma rates catch up with male rates. We hypothesize that by 12 years of age, certain early childhood home allergen exposures (cat) will decrease, while other exposures (cockroach) will increase risk of wheeze/asthma, eczema, and allergy. School-aged allergen exposures will increase airway symptoms in sensitized children. Secondly, allergen effects will be independent of other factors than may decrease (endotoxin, day care) or increase asthma or allergy risk (e.g., socioeconomic status, family history, smoking, body-mass index, stress, and for girls, early menarche). Thirdly, we hypothesize that asthma, eczema and hay fever will result from both IgE/Th2 and non-IgE/Th2 mediated mechanisms, as demonstrated in their associations with total IgE, allergen-specific IgE; IgG and IgG4 to cat measured at age 11. Finally, in a subset of 100 11 year old children with active asthma, eczema, or hay fever and 100 with no history of these syndromes, antigen (Der f 1, Fel d 1, Bla g 2) and LPS-stimulated lymphocyte production oflL-4, I1-13, IL-10, IL-6, TNF-alpha, and IFN-gamma, will also be measured. Understanding the evolution of the asthmatic immune response to allergens is an important key to developing better environmental or pharmacologic controls to either prevent or switch off the tendency to allergy and asthma in early life, before it results in chronic disease.